The main aims of the Neuropathology Core and its Tissue Resource (brain bank) component are: (1) to render final diagnoses on all ADRC research subjects who undergo autopsy based on the NIA-Reagan Institute guidelines (Neurobiol Aging Suppl S1-S2, 1997) together with Braak neurofibrillary pathology staging supplemented with stringent quantitative criteria that were developed at WUSM based on the 1985 NIA-Khachaturian consensus guidelines;(2) to collect, freeze, store, and distribute blood, plasma/serum, buffy coat DNA samples, and frozen CSF and CNS tissue collected at autopsy to WU and outside investigators in order to facilitate (funded) projects and pilot studies;(3) to maintain electronic databases of neuropathologic and Tissue Resource information in concert with the Clinical Core (Morris) to supplement the master information databases maintained by the Data Management Core (Miller) and the centralized NACC minimal database in Seattle;and (d) to carry out developmental research designed to advance diagnostic sensitivity and specificity of present and emerging brain markers in aging, Alzheimer's disease (AD) and related dementing disorders. Examples of current developmental research are the application of alpha-synuclein antibodies to detect and quantify Lewy and GCI-MSA pathology, development of a dual immunostain for a-beta and hyperphosphorylated tau proteins, and adapting tissue collection methods to support neurogenomic and proteomic analyses. Core leader McKeel heads the ADRC Tissue Committee, which assesses feasibility of research proposals that involve materials from the Tissue Resource. He is also a member of the ADRC Executive committee which approves proposals for scientific merit. McKeel consults with investigators using the Tissue Resource facility and supervises all tissue distribution on approved projects. The Core has extensively collaborated during the past five years. A current major undertaking is a NACC-sponsored collaboration among seven ADRCs to study the neuropathology of nondemented aging to better define preclinical AD;the Neuropathology Core is the central reference laboratory. The Core conducts weekly braincutting and microscopic case review conferences that are attended by medical and allied health students, residents, nurses and physicians. The Core maintains an "Alzheimer Tutorial" portion of the WUSM ADRC website that is widely used as a teaching resource. The Core leader is active nationally as head of the NACC Neuropathology Core Leaders subcommittee on Quality Assurance and Standards. McKeel leads the production of a Standardized Methods Manual for the QA/S committee.